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Perspectives
Importance of the cell cycle phase for the choice of the appropriate DSB repair pathway, for genome stability mintenance: the trans-S double-strand break repair model
Fabien Delacôte and Bernard S. Lopez
volume 7 | issue 1
1 January 2008Pages: 33 - 38
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A DNA double-strand break (DSB) is a highly harmful lesion which can lead to genome rearrangements. Two main pathways compete for DSB repair: homologous recombination (HR) and nonhomologous end-joining (NHEJ). Depending on the cell cycle phase, the choice of one DSB repair pathway over the other will secure genome stability maintenance or in contrast will increase the risk of genetic instability. HR with the sister chromatid is an efficient way to maintain genome stability, for damage occurring at a post-replication stage. However, in G1 checkpoint-defective cells, DSBs produced in the G1 phase and not repaired by NHEJ, can progress through S phase and be processed by HR in late S/G2 phase. We propose the “trans-S DSB repair” model to account for these data. In this situation HR cannot use the sister chromatid (which is also broken at the same locus) and is thus forced to use ectopic homologous sequences dispersed through the genome, increasing the risk of genetic instability. This shows that the two DSB repair pathways can compete through the cell cycle and underlines the importance of the association between the cell cycle checkpoint and the appropriate DNA repair pathway for genome stability maintenance.
Authors
Fabien Delacôte
Institut de Radiobiologie Cellulaire et Moléculaire; Fontenay aux Roses, France
Bernard S. Lopez
Institut de Radiobiologie Cellulaire et Moléculaire; Fontenay aux Roses, France